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WO1995022993A1 - Procede et dispositif permettant d'induire le retrecissement des voies aeriennes et/ou la production de salive - Google Patents

Procede et dispositif permettant d'induire le retrecissement des voies aeriennes et/ou la production de salive Download PDF

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Publication number
WO1995022993A1
WO1995022993A1 PCT/AU1995/000086 AU9500086W WO9522993A1 WO 1995022993 A1 WO1995022993 A1 WO 1995022993A1 AU 9500086 W AU9500086 W AU 9500086W WO 9522993 A1 WO9522993 A1 WO 9522993A1
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WO
WIPO (PCT)
Prior art keywords
substance
subject
airways
particles
group
Prior art date
Application number
PCT/AU1995/000086
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English (en)
Inventor
Sandra Doreen Anderson
Original Assignee
Central Sydney Area Health Service
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to DK95910331.8T priority Critical patent/DK0748228T3/da
Priority to DE122011000004C priority patent/DE122011000004I1/de
Priority to JP52202195A priority patent/JP3979660B2/ja
Priority to DE69536090T priority patent/DE69536090D1/de
Priority to EP95910331A priority patent/EP0748228B8/fr
Priority to CA002183471A priority patent/CA2183471C/fr
Application filed by Central Sydney Area Health Service filed Critical Central Sydney Area Health Service
Priority to AU17482/95A priority patent/AU682756B2/en
Priority to AT95910331T priority patent/ATE474583T1/de
Priority to NZ281522A priority patent/NZ281522A/en
Priority to US08/696,987 priority patent/US5817028A/en
Publication of WO1995022993A1 publication Critical patent/WO1995022993A1/fr
Priority to FR11C0002C priority patent/FR11C0002I2/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/0004—Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/04—Drugs for disorders of the respiratory system for throat disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/10—Expectorants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/12—Mucolytics

Definitions

  • the present invention relates to a method and device useful to provoke airway narrowing and/or the induction of sputum. More particularly the invention relates to the use of dry powdered substances to induce a change in the osmolarity of the airways to induce narrowing and/or the induction of sputum.
  • Asthma is a chronic inflammatory disease of the airways resulting in bronchial hyperresponsiveness to a wide variety of chemical, physical, and allergenic
  • This sensitivity is manifested by narrowing of the airways and a reduction in the forced expiratory volume in one second (FEV 1 ).
  • Bronchial provocation testing measuring changes in FEV 1 in response to inhaled stimuli, is well established as a technique for identifying and assessing the severity of airway hyperresponsiveness in persons suspected of having asthma (J Allergy Clin Immunol 1979; 64:1-250, Sterk et al Eur Respir J 1993,6(Supp 16):53-83..
  • Bronchial provocation testing with dry powders containing respirable particles of allergens has also been used to identify specific allergens in order to establish a relationship between exposure to the suspected agent and the onset of asthma. These are most commonly used to investigate occupational asthma.
  • allergens e.g. flour, red cedar wood dust, resins, gums
  • Hyperosmolar saline challenge appears to be a very useful technique to identify persons with current asthma and those who suffer exercise-induced asthma. It is also very useful to evaluate the drugs used in the treatment of asthma.
  • aerosols is that the person administering the challenge is also exposed to the aerosol as more than half of the amount generated by the nebuliser is expelled into the environment. Further the personnel are also exposed to saliva from the patient. There are also some difficulties encountered by the patient and these include the use of a nose peg, the production of a lot of saliva and the taste of salt.
  • the time taken to perform the challenge with a wet aerosol in a mild asthmatic or healthy control maybe 70 minutes. This comprises preparation of solution and apparatus (about 10 minutes), actual challenge time which for mild asthmatics may be up to 30 minutes, and finally post challenge cleaning and sterilisation (about 30 minutes).
  • wet aerosols of salt can be used for the purpose of increasing mucociliary clearance and inducing sputum in a subject.
  • This technique has been used since the 1970's by physiotherapists to enhance the clearance of secretions from the airways of subjects having cystic fibrosis and bronchitis.
  • the technique has been used with patients with HIV who are suspected of having Pneumocystis carinii which causes pneumonia and needs to be treated.
  • Sputum analysis in patients suspected of having tuberculosis is also known as a simple technique to look for the disease.
  • the present invention consists in a method for attempting to provoke airway narrowing in a subject comprising the steps of (a) causing the subject to inhale into the airways an effective amount of a substance capable of altering the osmolarity of airway surface liquid in the subject, which substance is in the form of a dispersible dry powder containing an effective proportion of particles of a respirable size, and (b) measuring in the subject a parameter indicative of the resistance to air flow of the subject's airways.
  • the present invention consists in a method for inducing sputum comprising the step of causing a subject to inhale into his or her airways an effective amount of a substance capable of altering the osmolarity of airway surface liquid, the substance being in the form of a dispersible dry powder containing an effective proportion of particles of a respirable size.
  • the present invention consists in a rupturable container containing an effective quantity of a substance capable of altering the osmolarity of airway surface liquid in a subject, the substance being in the form of a dispersible dry powder containing an effective proportion of particles of a respirable size.
  • a hyperosomolar challenge to a subject in the form of a dry powder rather than a wet aerosol enables the challenge to be administered through a conventional dry powder inhaler rather than through a nebuliser. This is highly advantageous as these inhalers are very cheap and are widely available.
  • the time to perform a challenge is halved as there is no cleaning, sterilising, maintenance or weighing involved in the use of the dry powder test. It would also appear that smaller doses of challenge substance need to be administered in the dry state to achieve a desired response than was required with that substance in the form of a wet aerosol.
  • airways includes both the upper airways of the nose and the lower airways of the lungs. While the invention is particularly applicable in the latter case it is also applicable in the former case for the detection of actual or incipient rhinitis, which may be due to dry air or allergens, and similar conditions. While the invention is hereinafter described with particular reference to the lower airways, this teaching could be applied with equal effect to the airways of the nose.
  • the substance to be inhaled may be any substance that is biologically compatible with the subject and is capable of altering, normally increasing, the osmolarity of the airway surface liquid of the subject.
  • the substance is a mineral salt or a sugar or sugar alcohol, more preferably it is selected from the group comprising salts of sodium or potassium, hexose and pentose sugars and their corresponding sugar alcohols. It is most preferred that the substance is selected from the group comprising sodium chloride, potassium chloride, mannitol and dextrose. Of the more preferred groups of substances sodium chloride and mannitol are the most preferred for their cheapness, their availability in the required particle size and their biological compatibility.
  • the substance is required to be inhaled into the airways, usually the first 8-12 generations, and an effective quantity is required to deposit on the surface of the airways.
  • the substance will make contact with the airways surface in the first twelve generations of the airways. For this to happen it is necessary for the inhaled substance to be present
  • respirable particle size is taken to mean a size that is sufficiently small that the particle will not settle out or impact against the subject's throat rather than be drawn into the airways of the subject's lungs . In practice it has been found that particles of less than about seven microns are respirable.
  • particles in the respirable range preferably comprise at least 10% of the substance by weight, more preferably at least 25%, even more preferably at least 40% and most preferably at least 50%.
  • respirable particles and non-respirable particles as the latter may induce coughing which will itself assist in the production of sputum.
  • the desired dose in either case will depend upon individual
  • the method for attempting to provoke narrowing may be used for testing subjects for their susceptibility to asthma.
  • the subject may be administered a series of challenges each of a higher dose of the selected substance. After each challenge the subject will be tested for airway narrowing, usually by measuring the forced expiratory volume in 1 second (FEV 1 ).
  • FEV 1 forced expiratory volume in 1 second
  • Other known methods for measuring parameters indicative of airway narrowing could equally well be used and airway resistance is usually used for the nose. It will be appreciated that in many cases there will be no narrowing which is
  • the parameter indicative of resistance to airflow after challenge is compared with the same parameter measured before the challenge to indicate the presence or absence of airway narrowing.
  • the substance is preferably packaged in a rupturable hard capsule, e.g. gelatin.
  • the capsules preferably contain doses of from 1 to 100mg, preferably 5 to 40mg in the case of challenge testing for asthma or rhinitis.
  • doses may prove desirable in subjects where airway narrowing is not a concern.
  • the present method for the induction of sputum may be used not only to collect sputum for analysis for the presence of viral or microbial pathogens but also in asthmatics to harvest inflammatory cells from the lung.
  • Figure 1 is a graph showing the percentage of predicted FEV 1 for healthy and asthmatic subjects before and after a dry powder challenge according to the present invention
  • Figure 2 is a graph showing the dose of dry powder relative to the dose of wet aerosol required to cause an asthmatic response in susceptible subjects
  • Figure 3 is a graph showing nasal airflow resistance before and after a dry powder challenge according to the present invention.
  • Figure 4 is a graph showing nasal airflow resistance before and after two successive dry powder challenges according to the present invention.
  • Example 2 performed a challenge with mannitol (Experiment 2) and 10 of these same subjects also performed a challenge with dry sodium chloride (Experiment 3) using a Ingelheim Inhalator (Boehringer Ingelheim).
  • Dry powder of sodium chloride or mannitol were prepared by spray drying an aqueous solution and milling, if necessary, so that particle size was in the respirable range ( ⁇ 7 microns).
  • the powder was produced by Genentech Inc, South San Francisco, California and sent in vials of 400 or 600 mg to our laboratory. There were two batches of sodium chloride and one of mannitol. Gravimetrically determined (change from known, known may be preferable) amounts (5, 10, 20 and 40 mg) of the dried powder were packaged in hard gelatin capsules (Gallipot, St Paul, Minnesota 55120) by our laboratory staff. In order to reduce any possibility of re-hydration, this was carried out under controlled air conditions (temperature 16-20 C relative humidity 40%).
  • Either the Halermatic or Ingelheim Inhalator was loaded with a capsule containing either 5, 10, 20, or 40 mg of sodium chloride or mannitol. The capsule was broken and the subject inhaled either once or twice to empty the capsule.
  • the inspiratory flow rate through the Halermatic was measured indirectly by measuring the change in pressure at the mouth ( Viggo-Spectromed DTX Disposable Pressure Transducer, Oxnard, CA, USA) during a maximal forced inspiration and values between 29-188L/min were recorded (Miniwriter Type WTR771A, Watanabe Instruments Corp). The low flow rates are due to the resistance of the device.
  • the inspiratory flow rate was measured by attaching it to a Minato Autospirometer (AS 800, Osaka, Japan) with the subject being asked to perform a maximum inspiratory manoeuvre through an empty Ingelheim Inhalator at the beginning of each study day.
  • the Minato AS 800 was calibrated using a rotameter and variable flow. Measurement of the response:
  • the FEV 1 was measured (Minato Autospirometer AS300, Minato Medical Science Co Ltd, Osaka, Japan) in duplicate, 60 seconds after the administration of the capsule.
  • the reduction in FEV 1 for each dose was expressed as a percentage of the value for FEVi measured 60 seconds after an inhalation manoeuvre had been made from the inhaler containing an empty capsule.
  • the challenge was started by giving an empty
  • the dose was started at 5 mg and was doubled with each exposure to a cumulative dose of 635 mg (5, 10, 20, 40, 2 ⁇ 40, 4 ⁇ 40, 4 ⁇ 40, 4 ⁇ 40mg). This protocol for dosing was varied by repeating the same dose if the subject had a
  • the subjects performed spirometry for at least 30 minutes following the completion of each challenge to assess spontaneous recovery.
  • the particle size was measured on a multistage liquid impinger (Astra Pharmaceuticals). This device measures particles in the range of 13 - 6.8 mm, 6.8 - 3.1 mm and ⁇ 3.1 mm. This device was used to measure the dose of sodium chloride that was in the respirable range ( ⁇ 6.8 mm). To do this 25 ml of sodium chloride or mannitol of known osmolarity was placed in each of the 3 stages of the impinger. Three 40 mg capsules of sodium chloride or mannitol were placed in either the Halermatic or an
  • the geometric mean and 95% confidence intervals have been calculated for the PD 20 for the wet aerosol challenge with 4.5% saline and the dry powder challenge with sodium chloride and mannitol.
  • a paired t-test was carried out after log transformation of the values.
  • Pre-challenge lung function (FEVi) was also compared using a paired t-test.
  • the relationship between the PD 20 to dry mannitol and sodium chloride and wet 4.5% saline was determined using a Piersons correlation coefficient. A value of p ⁇ 0.05 was taken as significant.
  • Figure 1 illustrates, for each test, the pre and end challenge values for FEVi expressed as a percentage of the predicted normal value. This demonstrates clearly that the airway response to the dry powder challenge was different between the healthy control subjects and the asthmatic subjects and that the airways of the asthmatic subjects narrowed in response to inhaling the dry powders (in all but one case).
  • Figure 2 illustrates the PD 20 to the dry powders of sodium chloride and mannitol in relation to the wet aerosol of 4.5% saline. This demonstrates that the subjects were somewhat more sensitive to the inhalation of the dry powders of sodium chloride and mannitol, compared with the wet aerosol of 4.5% saline delivered in a similar dose. This was particularly evident in Experiment 1 where there was a significantly lower dose of dry powder sodium chloride required to produce a 20% fall in FEVI compared with the wet aerosol (p ⁇ 0.02).
  • the mean time taken to perform the challenge with the dry capsule of mannitol was 10.0 ⁇ 3 min and varied from 6-14 minutes for the 13 subjects.
  • the advantages of the dry powder challenge over the wet aerosol challenge include; the faster time for challenge, the reduced necessity to clean apparatus and the potentially disposable nature of the inhalers.
  • Tikhomirov, Povlotska,& Zmievskaya (CC Number SU 1581325, kind A Date 900730 Week 9113 (Basic) from the Soviet Union have reported that a course of 10-15 daily inhalations of a NaCl aerosol (containing 70-80% of 3 micron particles with a density of 9-12 mg/cubic meter) given in a chamber with air velocity of 0.1-0.2 m/sec, 40-60 vol% of relative humidity at 16-18 degrees for periods gradually increasing from 6-15 min would increase remission of asthma of up to 1 year in 61.5% of cases.
  • the concentration of dry powder particles in our application is much higher, being
  • Transnasal pressure and flow were measured by posterior rhinomanometry. Flow was measured using a modified Sullivan mask (Rescare, Australia) attached to a No.2 Fleish pneumotachygraph. A firm air filled catheter was placed on the posterior tongue and sealed with the lips. This was referenced to the mask pressure and changes were measured with a Validyne MP45 pressure transducer (Validyne Corp, Northbridge, CA). Pressure and flow signals were recorded at a rate of 12 Hertz and were plotted simultaneously on a computer screen.
  • the salt was delivered to the nasal mucosa using a Spinhaler device (Fisons Pharmaceuticals) loaded with half the total dose.
  • the subject placed the loaded Spinhaler just inside one nostril and inhaled deeply. If the salt capsule was not empty after one inhalation, the subject performed another until the capsule was completely empty. The device was then reloaded and the other nostril was used.
  • FIGS. 3 & 4 show nasal resistance over 4 baseline measurements before challenge, followed by measurements made after the challenge.
  • Nasal resistance is expressed as cm H 2 O/L/sec. Both illustrate an increase in nasal resistance at 1 minute with a gradual fall to baseline over 15 minutes. This pattern is very similar to that seen with cold dry air both in terms of the degree of increase and the pattern of the subsequent fall to
  • Figure 4 shows results following inhalation of 40 mg, measurements for 20 minutes then a repeat dose of 40 mg.
  • Mucociliary clearance is assessed using a radioaerosol technique (99mTc-sulphur colloid is commonly used).
  • the radioaerosol should be generated with a nebuliser that produces droplets that have a mass median aerodynamic diameter (MMAD) of about 6 mm and a geometric standard deviation (GSD) under 2.
  • MMAD mass median aerodynamic diameter
  • GSD geometric standard deviation
  • a monodisperse aerosol would be ideal.
  • the radioaerosol should be delivered with a
  • Measurement of mucociliary clearance should start as soon as possible after the delivery of the radioaerosol.
  • the best way to assess mucociliary clearance is using a gamma camera. Collection of emission images with a gamma camera gives good information about the initial deposition of radioaerosol in terms of distribution and intensity. Serial anterior/posterior images for about one hour provide
  • Mucociliary clearance follows, usually, a biexponential pattern and curve fitting is commonly used to smooth the data.
  • the salt or mannitol is administered after the collection of the first images that are used to assess the initial deposition of the radioaerosol.
  • Dry powders of substances that have the potential to increase the osmolarity of the airway surface liquid, when inhaled in an adequate dose containing an adequate amount of respirable particles are suitable for use in bronchial provocation testing to identify persons with airway hyperresponsiveness consistent with asthma. These same substances can also be inhaled into the nose to identify persons with rhinitis. These same substances have the potential to be used to induce sputum and increase mucociliary clearance.

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Abstract

Procédé permettant de détecter une prédisposition à l'asthme chez une personne. La personne inhale une dose efficace de chlorure de sodium, de mannitol ou de toute autre substance susceptible de modifier l'osmolarité d'un liquide de surface des voies aériennes chez le sujet. La substance se présente sous forme d'une poudre sèche dispersible contenant une proportion efficace de particules de taille respirable. On effectue ensuite des mesures en vue de détecter un rétrécissement des voies aériennes du sujet, ce qui indiquerait une prédisposition à l'asthme. La même technique d'inhalation d'une poudre sèche peut être utilisée pour détecter une prédisposition aux rhinites chez une personne, pour induire la production de salive et favoriser la clairance mucociliaire.
PCT/AU1995/000086 1994-02-25 1995-02-23 Procede et dispositif permettant d'induire le retrecissement des voies aeriennes et/ou la production de salive WO1995022993A1 (fr)

Priority Applications (11)

Application Number Priority Date Filing Date Title
DE122011000004C DE122011000004I1 (de) 1994-02-25 1995-02-23 Pulver FÜR DIE PROVOKATION EINER VERENGUNG DER LUFTWEGE UND/ODER DER SPUTUMPRODUKTION
JP52202195A JP3979660B2 (ja) 1994-02-25 1995-02-23 気道狭窄の誘起及び／または痰の誘発の方法及び装置
DE69536090T DE69536090D1 (de) 1994-02-25 1995-02-23 Pulver FÜR DIE PROVOKATION EINER VERENGUNG DER LUFTWEGE UND/ODER DER SPUTUMPRODUKTION
EP95910331A EP0748228B8 (fr) 1994-02-25 1995-02-23 Poudre PERMETTANT D'INDUIRE LE RETRECISSEMENT DES VOIES AERIENNES ET/OU LA PRODUCTION DE crachat
CA002183471A CA2183471C (fr) 1994-02-25 1995-02-23 Procede et dispositif permettant d'induire le retrecissement des voies aeriennes et/ou la production de salive
DK95910331.8T DK0748228T3 (da) 1994-02-25 1995-02-23 Pulver til fremprovokering af en forsnæving af luftvejene og/eller frembringelse f spyt
AU17482/95A AU682756B2 (en) 1994-02-25 1995-02-23 Method and device for the provocation of air passage narrowing and/or the induction of sputum
AT95910331T ATE474583T1 (de) 1994-02-25 1995-02-23 Pulver für die provokation einer verengung der luftwege und/oder der sputumproduktion
NZ281522A NZ281522A (en) 1994-02-25 1995-02-23 Testing for asthma susceptability comprising inhalation of powder which can change airway size and measuring change in airflow
US08/696,987 US5817028A (en) 1994-02-25 1995-02-23 Method and device for the provocation of air passage narrowing and/or the induction of sputum
FR11C0002C FR11C0002I2 (fr) 1994-02-25 2011-01-21 Poudre permettant d'induire le retrecissement des voies aeriennes et/ou la production de crachat

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AUPM4114A AUPM411494A0 (en) 1994-02-25 1994-02-25 Method and device for the provocation of upper or lower airway narrowing and/or the induction of sputum
AUPM4114 1994-02-25

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WO1995022993A1 true WO1995022993A1 (fr) 1995-08-31

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US (1) US5817028A (fr)
EP (1) EP0748228B8 (fr)
JP (7) JP3979660B2 (fr)
KR (1) KR100385675B1 (fr)
CN (1) CN1075737C (fr)
AT (1) ATE474583T1 (fr)
AU (2) AUPM411494A0 (fr)
CA (1) CA2183471C (fr)
DE (2) DE122011000004I1 (fr)
DK (1) DK0748228T3 (fr)
ES (1) ES2349027T3 (fr)
FR (1) FR11C0002I2 (fr)
NZ (1) NZ281522A (fr)
PT (1) PT748228E (fr)
WO (1) WO1995022993A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996031221A1 (fr) * 1995-04-05 1996-10-10 Genentech, Inc. Preparation de formulations de chlorure de sodium pour aerosol
WO1998048875A1 (fr) * 1997-04-29 1998-11-05 The Procter & Gamble Company Procede applicable a l'administration de traitement halotherapeutique
US6339075B1 (en) 1997-06-30 2002-01-15 The University Of British Columbia Use of dextran and other polysaccharides to improve mucus clearance
EP2191718A1 (fr) * 1998-12-22 2010-06-02 The University of North Carolina at Chapel Hill Compose et usages permettant de traiter les maladies des voies respiratoires et de distribuer des medicaments contre lesdites maladies
MD4040C1 (ro) * 2009-12-09 2010-12-31 Институт Химии Академии Наук Молдовы Halocameră artificială de suprafaţă
MD4039C1 (ro) * 2009-11-05 2010-12-31 Институт Химии Академии Наук Молдовы Microsalină artificială de suprafaţă
MD4089C1 (ro) * 2009-11-18 2011-08-31 Институт Химии Академии Наук Молдовы Halocameră artificială de suprafaţă

Families Citing this family (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6235947B1 (en) * 1997-04-14 2001-05-22 Takeda Chemical Industries, Ltd. D-mannitol and its preparation
EA000968B1 (ru) 1996-04-16 2000-08-28 Байер Аг D-маннитол и его получение
US6634363B1 (en) 1997-04-07 2003-10-21 Broncus Technologies, Inc. Methods of treating lungs having reversible obstructive pulmonary disease
US7027869B2 (en) 1998-01-07 2006-04-11 Asthmatx, Inc. Method for treating an asthma attack
US7992572B2 (en) 1998-06-10 2011-08-09 Asthmatx, Inc. Methods of evaluating individuals having reversible obstructive pulmonary disease
US7921855B2 (en) 1998-01-07 2011-04-12 Asthmatx, Inc. Method for treating an asthma attack
US8181656B2 (en) 1998-06-10 2012-05-22 Asthmatx, Inc. Methods for treating airways
US7198635B2 (en) 2000-10-17 2007-04-03 Asthmatx, Inc. Modification of airways by application of energy
GB9826284D0 (en) * 1998-12-01 1999-01-20 Rhone Poulence Rorer Limited Process
US6926911B1 (en) * 1998-12-22 2005-08-09 The University Of North Carolina At Chapel Hill Compounds and methods for the treatment of airway diseases and for the delivery of airway drugs
WO2000062819A1 (fr) 1999-04-21 2000-10-26 1355540 Ontario Inc. Formulations pour detecter l'asthme
WO2001062264A2 (fr) * 2000-02-23 2001-08-30 The Procter & Gamble Company Procede d'halotherapie
US8251070B2 (en) 2000-03-27 2012-08-28 Asthmatx, Inc. Methods for treating airways
GB0014898D0 (en) * 2000-06-19 2000-08-09 Innovata Biomed Ltd Delivery system
US7104987B2 (en) 2000-10-17 2006-09-12 Asthmatx, Inc. Control system and process for application of energy to airway walls and other mediums
US6858615B2 (en) 2002-02-19 2005-02-22 Parion Sciences, Inc. Phenyl guanidine sodium channel blockers
JP2005535581A (ja) * 2002-05-02 2005-11-24 プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ 肺感染の拡大を制限する処方物
US20040226556A1 (en) 2003-05-13 2004-11-18 Deem Mark E. Apparatus for treating asthma using neurotoxin
US20050207983A1 (en) * 2004-03-05 2005-09-22 Pulmatrix, Inc. Formulations decreasing particle exhalation
WO2006125153A2 (fr) * 2005-05-18 2006-11-23 Pulmatrix Inc. Formulations pour la modification de proprietes biophysiques des muqueuses
AU2007294547A1 (en) * 2006-09-07 2008-03-13 Parion Sciences, Inc. Methods of enhancing mucosal hydration and mucosal clearance by treatment with sodium channel blockers and osmolytes
JP2010502739A (ja) * 2006-09-07 2010-01-28 パリオン・サイエンシィズ・インコーポレーテッド ナトリウムチャネル阻害剤及び浸透圧調節物質を用いた処置による粘膜水和及び粘液クリアランスの改善
US8714153B2 (en) * 2007-04-16 2014-05-06 Ric Investments, Llc Method for selecting a device adapted to treat disordered breathing
EP2211956A4 (fr) 2007-10-10 2014-07-09 Parion Sciences Inc Administration d'osmolytes par canule nasale
US8483831B1 (en) 2008-02-15 2013-07-09 Holaira, Inc. System and method for bronchial dilation
TWI432198B (zh) 2008-02-26 2014-04-01 Parion Sciences Inc 多芳香族鈉通道阻斷劑
AU2009244058B2 (en) 2008-05-09 2015-07-02 Nuvaira, Inc Systems, assemblies, and methods for treating a bronchial tree
AU2010229668C1 (en) 2009-03-26 2016-09-15 Pulmatrix Operating Co., Inc. Dry powder formulations and methods for treating pulmonary diseases
KR101722290B1 (ko) 2009-10-27 2017-03-31 호라이라 인코포레이티드 냉각 가능한 에너지 에미팅 어셈블리를 갖는 전달 장치
CA2780608C (fr) 2009-11-11 2019-02-26 Innovative Pulmonary Solutions, Inc. Systemes, appareils et procedes pour traiter un tissu et controler une stenose
US8911439B2 (en) 2009-11-11 2014-12-16 Holaira, Inc. Non-invasive and minimally invasive denervation methods and systems for performing the same
CN105640925B (zh) 2010-08-30 2019-08-16 普马特里克斯营业公司 干燥粉末配方及用于治疗肺部疾病的方法
EP2464346A1 (fr) 2010-08-30 2012-06-20 Pulmatrix, Inc. Méthodes de traitement de la mucoviscidose
MX354828B (es) 2010-09-29 2018-03-22 Pulmatrix Operating Co Inc Polvos secos de cationes metálicos monovalentes para inhalación.
AU2011314007B2 (en) 2010-09-29 2017-01-19 Pulmatrix, Inc. Cationic dry powders
US8945605B2 (en) 2011-06-07 2015-02-03 Parion Sciences, Inc. Aerosol delivery systems, compositions and methods
CA2838529C (fr) 2011-06-07 2020-03-24 Parion Sciences, Inc. Procedes de traitement
AR086745A1 (es) 2011-06-27 2014-01-22 Parion Sciences Inc 3,5-diamino-6-cloro-n-(n-(4-(4-(2-(hexil(2,3,4,5,6-pentahidroxihexil)amino)etoxi)fenil)butil)carbamimidoil)pirazina-2-carboxamida
SI2723176T1 (sl) 2011-06-27 2017-09-29 Parion Sciences, Inc. Kemijsko in metabolno stabilni dipeptid, ki ima močno aktivnost blokiranja natrijevega kanala
CA2865972C (fr) 2012-02-29 2022-01-04 Pulmatrix, Inc. Poudres seches pouvant etre inhalees
KR102109223B1 (ko) 2012-05-29 2020-05-11 패리온 사이언스 인코퍼레이티드 안구 건조 및 다른 점막 질환의 치료를 위한 나트륨 채널 차단제 활성을 보유하는 덴드리머 유사 아미노 아미드
WO2013184319A1 (fr) 2012-06-04 2013-12-12 Boston Scientific Scimed, Inc. Systèmes et procédés pour le traitement d'un tissu dans une voie de passage au sein d'un corps
US9592086B2 (en) 2012-07-24 2017-03-14 Boston Scientific Scimed, Inc. Electrodes for tissue treatment
US9272132B2 (en) 2012-11-02 2016-03-01 Boston Scientific Scimed, Inc. Medical device for treating airways and related methods of use
US9283374B2 (en) 2012-11-05 2016-03-15 Boston Scientific Scimed, Inc. Devices and methods for delivering energy to body lumens
BR112015014178A2 (pt) 2012-12-17 2017-07-11 Parion Sciences Inc compostos de 3,5-diamino-6-cloro-n-(n-(4-fenilbutil)carbamimidoil) pirazina-2- carboxamida
US9593084B2 (en) 2012-12-17 2017-03-14 Parion Sciences, Inc. Chloro-pyrazine carboxamide derivatives with epithelial sodium channel blocking activity
US9398933B2 (en) 2012-12-27 2016-07-26 Holaira, Inc. Methods for improving drug efficacy including a combination of drug administration and nerve modulation
HK1221175A1 (zh) 2013-04-01 2017-05-26 Pulmatrix Operating Company, Inc. 噻托溴铵乾粉
WO2015021314A1 (fr) 2013-08-09 2015-02-12 Boston Scientific Scimed, Inc. Cathéter expansible et procédé associé de fabrication et d'utilisation
CN104510726A (zh) * 2013-09-27 2015-04-15 张金华 一种用于清洁呼吸道系统的食盐干粉吸入剂
US9102633B2 (en) 2013-12-13 2015-08-11 Parion Sciences, Inc. Arylalkyl- and aryloxyalkyl-substituted epithelial sodium channel blocking compounds
KR102288656B1 (ko) 2020-12-02 2021-08-12 순천향대학교 산학협력단 천식 또는 천식 악화 진단용 pcr 키트 및 이를 이용한 천식 또는 천식 악화 진단을 위한 정보의 제공방법

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0177783A2 (fr) * 1984-09-11 1986-04-16 MECT Corporation Expectorants contenant l'acide N-acétylneuraminique et ses sels
DE3518665A1 (de) * 1985-05-23 1986-12-04 Hölter, Heinz, Dipl.-Ing., 4390 Gladbeck Salinenartiger holzfilter
AU7164587A (en) * 1986-03-04 1987-09-28 Chiesi Farmaceutici S.P.A. New pharmaceutical compositions for inhalation
AU7155991A (en) * 1990-01-24 1991-08-21 British Technology Group Limited Aerosol carriers
AU2746292A (en) * 1991-10-30 1993-05-06 Kenneth Roy Hanson Asthma and other allergies cure

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5623936A (en) * 1979-08-01 1981-03-06 Chest Corp Measuring apparatus of trachea hypersensitivity
WO1981001243A1 (fr) * 1979-10-30 1981-05-14 Riker Laboratories Inc Dispositif actionne par la respiration pour administrer des medicaments en poudre
DE3167567D1 (en) * 1980-06-06 1985-01-17 Fisons Plc Inhalation device for powdered medicaments
ES8206980A1 (es) * 1980-10-30 1982-09-01 Riker Laboratories Inc Un dispositivo para facilitar la inhalacion oral de medica- mentos en forma de polvo
CA1317194C (fr) * 1989-05-31 1993-05-04 Yves Cloutier Dispositif concu pour certains tests respiratoires, methode d'utilisation et generateur de particules ameliore
NL9002706A (nl) * 1990-12-10 1992-07-01 Pharmachemie Bv Inrichting ten gebruike bij het inhaleren van in staafvormige capsules verpakte poedervormige stoffen.
GB9101592D0 (en) * 1991-01-24 1991-03-06 Glaxo Group Ltd Compositions
DE4140689B4 (de) * 1991-12-10 2007-11-22 Boehringer Ingelheim Kg Inhalationspulver und Verfahren zu ihrer Herstellung
SE9203743D0 (sv) * 1992-12-11 1992-12-11 Astra Ab Efficient use
US5558085A (en) * 1993-01-29 1996-09-24 Aradigm Corporation Intrapulmonary delivery of peptide drugs
US5507277A (en) * 1993-01-29 1996-04-16 Aradigm Corporation Lockout device for controlled release of drug from patient-activateddispenser
CA2155933C (fr) * 1993-02-12 2000-04-04 James L. Levin Administration pulmonaire de scr1 et d'autres proteines inhibitrices du complement
US5497763A (en) * 1993-05-21 1996-03-12 Aradigm Corporation Disposable package for intrapulmonary delivery of aerosolized formulations
GB9408053D0 (en) * 1994-04-22 1994-06-15 Nat Heart & Lung Inst Pharmaceutical preparation
US5509404A (en) * 1994-07-11 1996-04-23 Aradigm Corporation Intrapulmonary drug delivery within therapeutically relevant inspiratory flow/volume values
US5522385A (en) * 1994-09-27 1996-06-04 Aradigm Corporation Dynamic particle size control for aerosolized drug delivery

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0177783A2 (fr) * 1984-09-11 1986-04-16 MECT Corporation Expectorants contenant l'acide N-acétylneuraminique et ses sels
DE3518665A1 (de) * 1985-05-23 1986-12-04 Hölter, Heinz, Dipl.-Ing., 4390 Gladbeck Salinenartiger holzfilter
AU7164587A (en) * 1986-03-04 1987-09-28 Chiesi Farmaceutici S.P.A. New pharmaceutical compositions for inhalation
AU7155991A (en) * 1990-01-24 1991-08-21 British Technology Group Limited Aerosol carriers
AU2746292A (en) * 1991-10-30 1993-05-06 Kenneth Roy Hanson Asthma and other allergies cure

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
DATABASE WPI Week 198737, Derwent World Patents Index; AN 1987-264036 *
DATABASE WPI Week 199131, Derwent World Patents Index; AN 1991-225137 *
DATABASE WPI Week 199231, Derwent World Patents Index; AN 1992-251539 *
EUROPEAN JOURNAL OF RESPIRATORY DISEASES,V ol. 66(2), 1985, B.G. SIMONSSON et al., "Acute and Long-term Airway Hyperreactivity in Aluminium-Salt Exposed Workers with Nocturnal Asthma". *
J ALLERGY CLIN IMMUNOL, vol. 64, 1979, pages 1 - 250
REMINGTON'S PHARMACEUTICAL SCIENCES, 17th. Edition 1985, MACK PUBLISHING CO, page 1835 - page 1601. *
STERK ET AL., EUR RESPIR J, vol. 6, no. 16, 1993, pages 53 - 83

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996031221A1 (fr) * 1995-04-05 1996-10-10 Genentech, Inc. Preparation de formulations de chlorure de sodium pour aerosol
US5747002A (en) * 1995-04-05 1998-05-05 Genentech, Inc. Preparation of sodium chloride aerosol formulations
AU717839B2 (en) * 1995-04-05 2000-04-06 Genentech Inc. Preparation of sodium chloride aerosol formulations
WO1998048875A1 (fr) * 1997-04-29 1998-11-05 The Procter & Gamble Company Procede applicable a l'administration de traitement halotherapeutique
US6339075B1 (en) 1997-06-30 2002-01-15 The University Of British Columbia Use of dextran and other polysaccharides to improve mucus clearance
EP2191718A1 (fr) * 1998-12-22 2010-06-02 The University of North Carolina at Chapel Hill Compose et usages permettant de traiter les maladies des voies respiratoires et de distribuer des medicaments contre lesdites maladies
MD4039C1 (ro) * 2009-11-05 2010-12-31 Институт Химии Академии Наук Молдовы Microsalină artificială de suprafaţă
MD4089C1 (ro) * 2009-11-18 2011-08-31 Институт Химии Академии Наук Молдовы Halocameră artificială de suprafaţă
MD4040C1 (ro) * 2009-12-09 2010-12-31 Институт Химии Академии Наук Молдовы Halocameră artificială de suprafaţă

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AU1748295A (en) 1995-09-11
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US5817028A (en) 1998-10-06
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FR11C0002I1 (fr) 2011-01-25
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